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Purpose

Ten to 15% of patients with breast cancer are HER2 positive, with treatment focused on targeting the HER2 receptor. Although these treatments are generally well tolerated, they are associated with an increased risk of cardiomyopathy. There are currently no treatments proven to prevent the cardiotoxicities associated with HER2-targeted therapy, but there is convincing preclinical data demonstrating that prophylactic treatment with a beta blocker (BB) and/or an SGLT2 inhibitor (SGLT2i) may each independently prevent cardiotoxicity and HER-targeted treatment interruptions. The proposed pilot study will assess the feasibility and preliminary efficacy and safety of therapy with both a beta blocker (carvedilol) and an SGLT2 inhibitor (empagliflozin), alone and in combination, in a population initiating HER2-directed therapy for HER2+ breast cancer. The hypotheses being tested in this study are: 1. It is feasible to recruit 20-40 patients over 6 months 2. There are no differences in tolerability and safety between participants taking carvedilol and/or empagliflozin and those receiving usual care.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Histologically or cytologically confirmed HER2+ breast cancer by ASCO/CAP guidelines of any clinical or pathologic stage. - Planning to commence standard of care HER2-directed therapy or started HER2-directed therapy within 6 months prior to randomization - At least 18 years of age. - Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 - For patients newly commencing HER2-directed therapy, left ventricular ejection fraction (LVEF) ≥ 50% up to 30 days prior to enrollment detected by echocardiogram. For patients already receiving HER2-directed therapy, LVEF ≥ 50% after the last cycle of therapy prior to enrollment. (Patient will be enrolled at the time of their next cycle after the echocardiogram.) - Systolic blood pressure ≥ 100 mmHg and resting heart rate ≥ 60 bpm. - eGFR > 30 mL/min/1.73m^2. - Women of childbearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. - Patients with an acceptable support system (as determined by the treating medical team). - Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria

  • Prior exposure to mantle cell lymphoma field radiation. - Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen as determined by the treating physician. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial. - Currently receiving treatment with SGLT2i or BB that cannot be stopped during the duration of study participation. Currently receiving non-dihydropyridine calcium channel blocker that cannot be transitioned to or used in combination with carvedilol. - Patients with untreated brain metastases requiring central nervous system directed therapy and interruption of systemic HER2 directed therapy (as determined by the treating medical team. - A known history of allergic reactions attributed to compounds of similar chemical or biologic composition to carvedilol, empagliflozin, or other agents used in the study. - Contraindication to carvedilol or empagliflozin at the discretion of the investigator such as: - Bronchial asthma or related bronchospastic conditions where BB would be contraindicated - Second- or third-degree atrioventricular (AV) block - Sick sinus syndrome - Severe bradycardia (unless permanent pacemaker in place) - In cardiogenic shock or decompensated heart failure requiring the use of IV inotropic therapy - Severe hepatic impairment in setting of cirrhosis that prevents use of carvedilol - Uncontrolled intercurrent illness including, but not limited to ongoing or active infection or uncontrolled cardiac arrhythmia. - Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Factorial Assignment
Intervention Model Description
This is a 2x2 factorial, open-label, randomized pilot study. Patients will be randomized on a 1:1 basis to either carvedilol or no carvedilol, and again on a 1:1 basis to either empagliflozin or no empagliflozin, meaning that there are four arms: - Arm 1: carvedilol - Arm 2: empagliflozin - Arm 3: carvedilol + empagliflozin - Arm 4: usual care
Primary Purpose
Prevention
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm 1: Carvedilol BID 		Carvedilol by mouth twice per day (BID) for 12 weeks.
  • Drug: Carvedilol
    6.25 mg with food
    Other names:
    • Coreg
Experimental
Arm 2: Empagliflozin QD 		Empagliflozin by mouth daily (QD) for 12 weeks.
  • Drug: Empagliflozin
    10 mg in the morning with or without food
    Other names:
    • Jardiance
Experimental
Arm 3: Carvedilol BID + Empagliflozin QD 		Carvedilol by mouth twice per day (BID) for 12 weeks and empagliflozin by mouth daily (QD) for 12 weeks.
  • Drug: Carvedilol
    6.25 mg with food
    Other names:
    • Coreg
  • Drug: Empagliflozin
    10 mg in the morning with or without food
    Other names:
    • Jardiance
No Intervention
Arm 4: Usual Care 		No medications.

Recruiting Locations

Washington University in St. Louis and nearby locations

Washington University School of Medicine
St Louis 4407066, Missouri 4398678 63110
Contact:
Joshua Mitchell, M.D., MSCI, FAC, FICOS
314-494-3124
jdmitchell@wustl.edu

More Details

NCT ID
NCT06844669
Status
Recruiting
Sponsor
Washington University School of Medicine

Study Contact

Joshua Mitchell, M.D., MSCI, FAC, FICOS
314-494-3124
jdmitchell@wustl.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.